Thanks Alex. I agree re Pall. He does I think suggest that the initial 'cause' could be one thing or many different things, but has never really focused on that, but rather on the 'cycle' he that he says keeps us from getting well. I agree too that both his and Rich's theories seem to mesh well, but there is also perhaps some missing pieces, which may be genetic expression-related or other liver detox pathway issues...

Regarding 'iron catalysis' -- does this mean that iron stores might be used up in the process, if adb12 is low?

Thanks in advance.

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Iron is not used up in such catalysis I think. So it wont deplete iron.

Do you think, if the Wheatley paper is correct, that it probably wouldn't be a bad idea to give supplementing adenosyl cobalamin and BH4 a try? Would that put our macraphages and NK cells at more or at less risk? Wasn't completely sure of what you meant regarding their vunerability. Thanks.

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Macrophages might be vulnerable to NO, and NK cells are a little like macrophages, but their response is jsut a guess. I need to do more investigation, much more probably.

I am considering testing adenosyl cobalamin directly, though my methyl cobalamin should at least partially correct an adenosyl B12 problem. BH4 has been suggested before, by Rich and Marty I think. Does anyone know what people have tried to boost BH4 levels?

Thanks for the link dannybex. I am aware of many trace elements having minor or non-understood impact because we dont resaerch them much. However I do not see a reason to use this in ME. It might help, but who knows? If a person has a specific reason, based on their own case history, then OK. I am just concerned that people might be trying this for ME without a specific reason. Personally I would be very wary of taking boron.

However, just because something is toxic does not mean its not good for us at microdoses. Chromium is a very good example of that.

I would be cautious with Boron. Dose makes the poison. 200mcg of Boron is very different than 20mg of Boron. That I FELT the difference about an hour into the first 2.5mg of the capsule, 50mcg of Boron and who knows how much actually absorbed in that time, made a noticable difference over a 50mg sublingual dose of Source Naturals dibencozide a week earlier which made no noticable difference at any time.

Just where it comes to play I don't know. I will tell you that before AdoCbl and l-carniitine fumarate, I could not heal muscle, recover from exercise or grow muscle. I put on about 50 pounds of muscle with rehab levels of exercise and walking in a bout 2 years. I also took off a toftal of 85 pounds of water, half when I added the l-carnitine and the orther half when I was able to up the Metafolin to levels that ended paradoxical folate deficiency most of the time. The Deadlock Quartet appears to be enhanced by a little Boron, and I don't know why. I'm sure others norticed the difrference too no matter what their reasoning would me. I doubt that testosterone would make a noticable difference in 1 hour. I've been on testosterone for 9 years now and it NEVER did what AdoCbl with or without Boron did.

The big difference with the active b12 protocol is that amazingly rapid decline of inflammation compared to HyCbl.. Dr Wheatley has a sense of humor. Her fist 3 papers on Hycbl and inflammation control were the Scarlet Pimpernil papers. As AdoCbl is predicted to be radically more effective thanb Hycbl, AND IT IS. I've been saying 100 to 10,000 times more effective (MeCbl and AdoCbl combined) than the inactive and that is radical. That is why healing turns on in 3 days and goes like gangbusters for a year or 3.

I wonder if the 200 mcg of boron makes no difference at all. I use concentrace minerals and a teaspoon of that contains 370 mcg of boron. Tap water might have more than 200 mcg of boron per cupful in some areas.

Anabol Naturals ADB12 is very strong. I took Source Naturals ADB12 for about 4-5 months and liked it, but never got the strong reaction I've had to Anabol brand. Maybe Anabol brand is a 5 star adb12, and Source Naturals is not.

I wonder if the 200 mcg of boron makes no difference at all. I use concentrace minerals and a teaspoon of that contains 370 mcg of boron. Tap water might have more than 200 mcg of boron per cupful in some areas.

Anabol Naturals ADB12 is very strong. I took Source Naturals ADB12 for about 4-5 months and liked it, but never got the strong reaction I've had to Anabol brand. Maybe Anabol brand is a 5 star adb12, and Source Naturals is not.

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Hi Pela,

I have never been able to come up with a rating for Source Naturals. I suspect you are right, the Anabol Dibencoplex is the 5 star AdoCbl for now. Anything else has to equal or exceed that to have the same rating. The Boron would only possibly make a difference for those not getting it in their snowmelt runoff water for instance. You get more Boron in the mineral concentrate than I get total. I am considering some titration trials for myself.

The facination in this paper for me is that it gives a theoretical foundation for why the active b12 protocol is so radically more effective. While I can't pretend to understand even half of the biochemistry this fits in every way. The dose, required, and this larger dose idea, has been in every paper Wheatley has written that I have read so far, on HyCbl as well, is that unbound b12 is critical to having this higher effect. Also, with titrations by people here it is clear that 100mcg absorbed daily is sufficient to turn on all but CNS levels of healing generally, and that 100mcg is some multiples of the amount of HTCII cobalamin which only constitutes about 20% of bound serum cobalamin with HTCI beinbg 80% headed for the liver, not the tissues. This requirement for the higher doses for "natural healing" requires distribution by diffusion and can start in 5 minutes with "radically" more effectiveness of adnosylcobalamin than for Hycbl which is what is seen over and over.

So the functions now on adenosylcobalamin are:

Anti-inflammatory in a complete fashion by diffusion

Processing fatty acids for use in making myelin for the nerves

Mitochondrial functioning producing ATP all mitochondrial recptors occupied, happens in days with mg of adenosylcobalamin, in weeks at 100mcg per day, rest of your life at 3-10mcg in active absortion/transport system per day

With L-carnitine fumararte makes more ATP and promotes dopamine production (by effect, method not known to me)

I had a clear start up response when I started boron, and have continued to need 6 mg daily so far. I may have an absorption issue--all I know is so far I need this much.

I am working up my dosages and am finally seeing some good progress. I am taking 15 mg Deplin in divided doses, 7.5 mg MB12 injections twice a day with several ET sublinguals in between (the shot seems to "run out" and I start to crash about 5 hours later) and in the evenings. So I'm continuing to increase the shot dosages. I'm taking Source Naturals ADB12 4-5 daily--and this seems important to my progress, I'll soon switch to Anabol and my doctor is trying to get injectable ADB12 for me. LCF was very important initially but I no longer need it or is it helpful. I use prescription strength potassium.

Anyway the boron may have enabled me to increase doses of AD and MB12. I take lots of other supports, I won't list them all. My point is to add this experience to this thread about the importance of boron and more ADB12.

I have recently been using the Anabol Dibecoplex adb12. It also includes Boron which is an essential trace element in it's utilization in the body. I empty a quater of a cap onto a spoon and then drop it along my lower lip and gums aqnd it takes 2-3 hours to absorrb. I do that 4 times ne day a week and that maitains me in equilibrium becasue the turnover ofrate is slow. This recent paper may point the wqay for inflammation control being more effective if taken in smakller doses daily.. I was doing the one larger dose a week to get it inth the CSF/CNS. My daughter found every day to be essential. Others have found that too so we were wondering what could account for that.

Is taking powder from capsules and holding them along your lower lip and gum an effective alternative to using sublinguals for other supplements? I know there's people here who are concerned about the mannitol and sorbitol in sublinguals for various other supplements.

Using methylfolate to boost BH4 might work, but it also creates theoretical and practical issues. First, it generates additional impetus in other pathways. Second, if the problem is with generation of BH4 this might not fix it. Being able to boost BH4 directly might be a better choice for a subset of patients. We really need the science to be done on this, but in the absence of science I think knowing if BH4 is beneficial by direct supplementation could tell us a lot. Its used to treat PKU, so there are drug forms of it, but this would definitely be off label use. Simlarly there are supplements that boost BH4 though I have forgotten most of this. I was looking at it some years ago.

Finally, some of us do not improve on methyl folate, or get worse. That does not rule out possible improvement on BH4. In the absence of decent science on this the only way to be sure is trial and error - suck it to see if its a lemon.

I have a question that I have not seen asked yet: I have the solgar metafolin and my question is are we suppose to take it sublingualy too? I have been but have not seen that it is required?
I also have methyl mate from yaskow and it is in liquid form, I have sniffed this up each nosrtil and am wondering if Freddd thinks this is advantageous for another surface of absorption, nasal passages?
Thank you,
Pinky

BH4 can be useful for people with MTHFR A1298c SNP which does not reduce methylfolate production but inhibits BH4 production (BH4 != TH4), thus impacting dopamine and serotonin production among other things.

People with MTHFR A1298c have to be careful they don't overdrive with methylfolate since the feedback inhibition by SAMe is reduced at the MTHFR enzyme assuming no other relevant mutations. COMT and VDR SNP status also complicate things further.

Still methyfolate has its uses of course if a partial block exists for other (functional) reasons. This is all moot if the person has other MTHFR mutations which I suspect most people on these forums do.

I have never been able to come up with a rating for Source Naturals. I suspect you are right, the Anabol Dibencoplex is the 5 star AdoCbl for now. Anything else has to equal or exceed that to have the same rating. The Boron would only possibly make a difference for those not getting it in their snowmelt runoff water for instance. You get more Boron in the mineral concentrate than I get total. I am considering some titration trials for myself.

The facination in this paper for me is that it gives a theoretical foundation for why the active b12 protocol is so radically more effective. While I can't pretend to understand even half of the biochemistry this fits in every way. The dose, required, and this larger dose idea, has been in every paper Wheatley has written that I have read so far, on HyCbl as well, is that unbound b12 is critical to having this higher effect. Also, with titrations by people here it is clear that 100mcg absorbed daily is sufficient to turn on all but CNS levels of healing generally, and that 100mcg is some multiples of the amount of HTCII cobalamin which only constitutes about 20% of bound serum cobalamin with HTCI beinbg 80% headed for the liver, not the tissues. This requirement for the higher doses for "natural healing" requires distribution by diffusion and can start in 5 minutes with "radically" more effectiveness of adnosylcobalamin than for Hycbl which is what is seen over and over.

So the functions now on adenosylcobalamin are:

Anti-inflammatory in a complete fashion by diffusion

Processing fatty acids for use in making myelin for the nerves

Mitochondrial functioning producing ATP all mitochondrial recptors occupied, happens in days with mg of adenosylcobalamin, in weeks at 100mcg per day, rest of your life at 3-10mcg in active absortion/transport system per day

With L-carnitine fumararte makes more ATP and promotes dopamine production (by effect, method not known to me)

So where and how does Boron help this? Where in any of these chains?

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Question: Isn't the Anabol Dibencoplex a capsule? I thought oral bioavailability for Adb12 is generally low, i.e. it disassociates readily in the gut.

I am only asking since for some reason the Source Naturals brand makes me kind of spacey and tired for an hour or so when I take 1/5-1/4 tablet sublingually under the upper lip. Maybe it is something else in the Source Naturals that bugs me. So I am looking for alternatives. Or maybe I am missing some cofactor like carnitine or something.

On that note do you suggest spreading adb12 throughout the day in 2-3 doses or all at once? Still trying to work out what is best.

Also I think the effect of carnitine on dopamine is observed for acetyl-l-carnitine since it is the only one that is blood brain barrier penetrable.

And yes 200 mcg of boron is pretty small compared to the mg's stuffed into vitamin supplements. Personally I didn't do well at all on 2-3 mg of boron when I took it back in the day.

The haem-centered NOS catalysis (hypothesized to be the back-up reaction) needs BH4 but also FAD and FMN (both vit B2).
The adenosylcobalamin reaction also needs BH4.

But for this second (or first) path to work you would need tetrahydrobiopterin in proportion to adenosylcobalamin.
Where do you find this? Is it easily depleted by taking adenosylcobalamin?
Or is there a recycling mechanism (dependent on?)?

"Defects in the regeneration of the cofactor tetrahydobiopterin (BH4) account for a small fraction of PKU cases. Such cases are sometimes identified as "malignant" PKU, because of the progressive deterioration in neurological function which cannot be alleviated by simple dietary restriction in phenylalanine intake. These cases may be distinguished from the classical form of PKU which is due to a defect in the enzyme phenylalanine hydroxylase (PAH). There are several possible causes of a defect in biopterin metabolism, and the consequences of such a defect can be profound, extending beyond phenylketonuria to defects in neurotransmission. Such cases can be better understood by referring to the biosynthetic pathway of tetrahydrobiopterin:".....http://www.uic.edu/classes/phar/phar332/Clinical_Cases/aa metab cases/PKU Cases/bioh4.htm

It could be that the tetrahydrobiopterin is missing, not the adenosylcobalamin. Or both. Or first the one (lack of adenosylcobalamin) then resorting to the first reaction (inducing a lack of B2) then a total crash if there is no more BH4?

Since tetrahydrobiopterin is needed to get rid of phenylalanine, and the modern diet is overwhelming us with that, and that it is needed for making adrenalin (which we consume at an alarming rate through stress and our way of life) it could very well be that there are much more people suffering from BH4 deficiency that thought previously.

How come changing the diet is not sufficient? Maybe BH4 deficiency is a life-saving adaptation. Maybe the body goes in another mode for survival? And stays there? An epigenetic switch?

Enough for today and many thanks Freddd for bringing this up!

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Ahh now this was an interesting post.

Some of us as you know have homo or hetero-zygote mutations of MTHFR a1298c which can lead to problems making BH4. Also if I remember correctly BH4 is used heavily to detoxify ammonia from the body that cannot be already cleaned up by glutamine synthetase. BH4 is critical to dopamine and sertonin production and NOS. But it is also recycled from BH2 via DHFR (see the following link: http://www.ncbi.nlm.nih.gov/pubmed/19666465)

So it wears many hats in the body and can be drained from multiple reactions creating a possibly delicate equilibrium. The inflammation link via balancing of various nitric oxide forms is quite eye opening especially since it brings in all the mast cells issues.

What I find fascinating is I wonder if taking a significant dose of adb12 all at once sublingually actually temporarily depletes BH4. The reason I bring this is up is from personal experience adb12 initially always makes me tired for 1-2 hours and a bit spacey. But in addition my mood gets bad during that time. Like lazy depressed hate the world bad ...
But then with time I rebound and hours later I feel MUCH better.

Maybe I need to split the adb12 doses up smaller into 2-3 doses per day and also go back and re-examine some of Dr Yasko et al. research on BH4 deficiencies.

Your epigenetic hypothesis is tantalizing btw ... that would really affect a lot of pathways at the same time and push the person into an undesirable metastable state. I wonder if my auto-immune disease forced the issue in some way or alternatively was caused in part by a failure in this part of the biological pathways. Hmmm.

Still methyfolate has its uses of course if a partial block exists for other (functional) reasons. This is all moot if the person has other MTHFR mutations which I suspect most people on these forums do.

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Yes, I have the C677T mutation, but not the A1298C, so I need to take methylfolate. Still, I have a lot of neurological problems though, which would indicate issues with BH4, so I am not really sure what is going on.